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Biomedical subjects

C Cremers

Publications and source records attributed to C Cremers.

At least 19 recordsLinked to original sources
PubMed2004

Audiometric evaluation of an attempt to optimize the fixation of the transducer of a middle-ear implant to the ossicular chain with bone cement.

Typically, an implantable hearing device consists of a transducer that is coupled to the ossicular chain and electronics. The coupling is of major importance. The Vibrant Soundbridge (VSB) is such an implantable device; normally, the VSB transducer is fixed to the ossicular chain by means of a special clip that is crimped around the long process of the incus. In addition to crimping, bone cement was used to optimize the fixation in six patients. Long-term results were compared to those of five controls with crimp fixation alone. To assess the effect of bone cement (SerenoCem, Corinthian Medical Ltd, Nottingham, UK) on hearing thresholds, long-term post-surgery thresholds were compared to pre-surgery thresholds. Bone cement did not have any negative effect. Next, to test the hypothesis that aided thresholds might be better with the use of bone cement, aided thresholds were studied. After correction for the severity of hearing loss, only a small difference was found between the two groups at one frequency, viz. 2 kHz. It was concluded that there was no negative effect of using bone cement; however, there is also no reason to use bone cement in VSB users on a regular basis.

Adult↗
PubMed2000

Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.

Usher syndrome type IIa (USHIIa) is an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa. This disorder maps to human chromosome 1q41. Recently, mutations in USHIIa patients were identified in a novel gene isolated from this chromosomal region. The USH2A gene encodes a protein with a predicted molecular weight of 171.5 kD and possesses laminin epidermal growth factor as well as fibronectin type III domains. These domains are observed in other protein components of the basal lamina and extracellular matrixes; they may also be observed in cell-adhesion molecules. The intron/exon organization of the gene whose protein we name "Usherin" was determined by direct sequencing of PCR products and cloned genomic DNA with cDNA-specific primers. The gene is encoded by 21 exons and spans a minimum of 105 kb. A mutation search of 57 independent USHIIa probands was performed with a combination of direct sequencing and heteroduplex analysis of PCR-amplified exons. Fifteen new mutations were found. Of 114 independent USH2A alleles, 58 harbored probable pathologic mutations. Ten cases of USHIIa were true homozygotes and 10 were compound heterozygotes; 18 heterozygotes with only one identifiable mutation were observed. Sixty-five percent (38/58) of cases had at least one mutation, and 51% (58/114) of the total number of possible mutations were identified. The allele 2299delG (previously reported as 2314delG) was the most frequent mutant allele observed (16%; 31/192). Three new missense mutations (C319Y, N346H, and C419F) were discovered; all were restricted to the previously unreported laminin domain VI region of Usherin. The possible significance of this domain, known to be necessary for laminin network assembly, is discussed in the context of domain VI mutations from other proteins.

Amino Acid Sequence↗
PubMed2000

Histopathologic features of the temporal bone in usher syndrome type I.

Temporal bones of 2 patients with Usher syndrome type I were examined using light microscopy. In both patients, findings from histopathologic examination of the cochlea were characterized by degeneration of the organ of Corti, which was most marked in the basal turn, atrophy of the stria vascularis, and a decrease in the number of spiral ganglion cells. The cochlear nerve appeared to be diminished. The sensory epithelium of the saccular and utricular maculae of patient 1 was normal for age. The left temporal bone of patient 2, classified as Usher syndrome genetic subtype USH1D or USH1F, demonstrated the typical signs of severe cochleosaccular degeneration. Present cases and cases from the literature were reviewed in search of an explanation for the above-described differences in histologic findings.

Aged↗
PubMed2000

The phenotype of DFNA13/COL11A2: nonsyndromic autosomal dominant mid-frequency and high-frequency sensorineural hearing impairment.

OBJECTIVE: To study nonsyndromic progressive sensorineural hearing impairment in patients with a COL11A2 mutation (DFNA13) in a Dutch kindred. STUDY DESIGN: Survey. SETTING: Department of otorhinolaryngology of a university hospital. PATIENTS: Twenty-one living members of a Dutch family (150 relatives in 5 generations; 49 were studied) with autosomal dominant nonsyndromic sensorineural hearing impairment showed linkage to the DFNA13 locus. Mutation analysis revealed a missense mutation in the COL11A2 gene. METHODS: History was taken, hearing threshold levels were measured in all affected persons, and penetrance was evaluated. Longitudinal analysis (using linear regression analysis of threshold-on-age data) was possible in only 1 case. Cross-sectional analysis comprised the comparison of threshold levels between different generations of the family. Also, hearing thresholds were corrected for median presbyacusis to find out whether the hearing impairment characteristic of this trait is stationary or progressive. Vestibular functions were evaluated with electronystagmography, by use of rotatory and caloric tests. RESULTS: Most of the affected persons dated their first hearing impairment symptoms to the second to third decade of life. A possibly reduced penetrance was found. Anamnestically, 4 affected persons had hearing impairment symptoms from early childhood onward. Longitudinal analysis in the proband (IV26) revealed the exceptional combination of congenital offset and substantial early progression. Most of the threshold levels differed significantly between the frequencies within each age group and, at the high frequencies (2-8 kHz), between the two age groups covered by generations IV and III (ages 30-38 years and 58-74 years, respectively); the latter could be attributed to presbyacusis. Various caloric abnormalities, including areflexia, were found in about half (8/17) of the tested subjects with sensorineural hearing impairment. CONCLUSIONS: Correction for age, hearing impairment-presumably present and stationary from an early age onward-showed the worst or second-worst threshold usually at 1, 2, and 6 kHz (3540 dB) or 8 kHz (50 dB), whereas the best or second-best threshold was found at 0.25 to 0.5 and 4 kHz (25 dB). Presbyacusis, presumably from the fourth decade of life onward, caused a change of the typically shaped audiogram described as midfrequency hearing impairment with additional high-frequency impairment.

Adult↗
PubMed2000

Non-syndromic autosomal dominant progressive non-specific mid-frequency sensorineural hearing impairment with childhood to late adolescence onset (DFNA21).

An autosomal dominant trait of progressive, non-syndromic, non-specific mid-frequency sensorineural hearing impairment was identified in a Dutch family. Many affected family members (n = 21) were identified, among whom seven out of nine relatives aged < 30 years do not show pure mid-frequency hearing impairment, which suggests variable expression. Regression analysis was used to evaluate the age-related hearing threshold data in a cross-sectional analysis in 24 affected patients and in a longitudinal analysis in five of these. At all frequencies, progression in hearing impairment (i.e. the regression coefficient) was significant and fairly similar: the pooled value was about 1.0 dB/y. There was no significant (i.e. not =0 dB) offset threshold (i.e. Y intercept at age 0) found at any frequency. The regression lines could be pooled for the low frequencies (0.25-0.5 kHz) and the mid/high frequencies (1-8 kHz) and this produced apparent onset ages of about 3 and 4 years and annual threshold increases of 0.75 and 1.1 dB/y, respectively. In most patients there is a relatively late onset age (maximum in the range of at least 25-45 years). However, based on the longitudinal analysis of a patient from the age of 4 years onwards in some patients sensorineural hearing impairment might be congenital/prelingual. Oculo-vestibular function was found to be normal. Results from linkage studies tentatively position the underlying gene defect telomeric to the repositioned DFNA13 locus at chromosome 6p21-22.

Adult↗
PubMed1999

The cochlear nuclei in two patients with Usher syndrome type I.

HYPOTHESIS: Does long-term sound deprivation lead to degeneration of the cochlear nuclei in two Usher type I patients? METHODS: The cochlear nuclei of these patients were morphometrically analyzed and compared with two age-matched controls. Routine autopsy of the brainstems was performed before the design of this study was known. During this procedure, the ventral cochlear nucleus (VCN) can easily be damaged. Five partially damaged VCN could nevertheless be analyzed for this study, including the right VCN of Usher patient 1 and both VCN of Usher patient 2. Using 15 microm thick serial paraffine sections of the cochlear nuclei, estimates of volume, neuronal densities, number of cells and mean cell diameter of the dorsal cochlear nucleus (DCN) and VCN were obtained. RESULTS: This study presents unique material of the cochlear nuclei in two patients with Usher syndrome type I. Data regarding volume and total cell number of the VCN are influenced by the absence of a part of the VCN. Results suggest a decrease in mean cell diameter of the VCN in Usher patients. Other parameters of the VCN and DCN, however, showed no major differences between Usher type I patients and controls. CONCLUSION: Only minor degenerative changes are apparent in the cochlear nuclei of two patients with Usher type I, who were deprived of acoustic stimuli since birth.

Aged↗
PubMed1999

Hearing impairment related to age in Usher syndrome types 1B and 2A.

OBJECTIVE: To evaluate hearing impairment in 2 common genetic subtypes of Usher syndrome, USH1B and USH2A. DESIGN: Cross-sectional analysis of hearing threshold related to age in patients with genotypes determined by linkage and mutation analysis. SETTING: Otolaryngology department, university referral center. PATIENTS: Nineteen patients with USH1B and 27 with USH2A were examined. All participants were living in the Netherlands and Belgium. MAIN OUTCOME MEASURE: Pure tone audiometry of the best ear at last visit. RESULTS: The patients with USH1B had residual hearing without age dependence, with minimum thresholds of 80, 95, and 120 dB at 0.25, 0.5, and 1 to 2 kHz, respectively. Mean thresholds of patients with USH2A were about 45 to 55 dB better than these minimum values. Distinctive audiographic features of patients with USH2A were maximum hearing thresholds of 70, 80, and 100 dB at 0.25, 0.5, and 1 kHz, respectively, only at younger than 40 years. Progression of hearing impairment in USH2A was 0.7 dB/y on average for 0.25 to 4 kHz and could not be explained by presbyacusis alone. CONCLUSIONS: The USH1B and USH2A can be easily distinguished by hearing impairment at younger than 40 years at the low frequencies. Hearing impairment in our patients with USH2A could be characterized as progressive.

Adult↗
PubMed1999

Diagnosis and management strategies in congenital atresia of the external auditory canal. Study Group on Otological Malformations and Hearing Impairment.

This consensus report represents a distillation of current opinion regarding diagnosis and management of congenital aural atresia. It also takes into account the philosophical differences which exist in Europe. Congenital aural atresia requires prompt diagnosis, genetic counselling and an early assessment of hearing. In bilateral atresia, early amplification with a bone conduction hearing aid is essential for proper speech development. Further rehabilitation in bilateral cases is managed with surgical reconstruction in selected patients or by implantation of a bone-anchored hearing aid. Atresia repair surgery is worthwhile if proper patient selection is made by use of stringent audiological and radiological criteria and state of the art surgery is performed. The divergent views concerning indications, ideal age for surgery and surgical approach to achieve better hearing are discussed. Review of the literature demonstrated that even in the hands of the best surgeons a mean hearing gain of only 20-25 dB is achieved in atresia Type II, with 30-35 dB in Type I. Therefore, surgical reconstruction should only be done in the more favourable cases where post-operative hearing of <25-30 dB is attainable. Less favoured patients should be helped with bone-anchored hearing aids, as this type of surgery does not interfere with the future use of new techniques.

Ear Canal↗
PubMed1998

Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa.

Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.

Amino Acid Sequence↗
PubMed1998

Nonsyndromic autosomal dominant progressive sensorineural hearing loss: audiologic analysis of a pedigree linked to DFNA2.

An analysis was performed of the regression of the individual hearing threshold on age in the affected persons in a six-generation Dutch family with nonsyndromic autosomal dominant sensorineural hearing loss, which showed linkage to the DFNA2(1p34) region, similar to at least four previously reported nonrelated families. The offset threshold was significantly higher at the high frequencies (around 30 dB at 2 to 8 kHz) than at the lower ones (approximately 0 dB at 0.25 to 1 kHz). Hearing impairment at the higher frequencies may therefore have been present already at birth or in early childhood. The regression coefficient, or the 'annual threshold increase,' expressed in dB/y, was about 1 dB/y on average, but the higher frequencies (1 to 8 kHz) showed significantly more rapid progression than the lower frequencies (0.25 to 0.5 kHz).

Aging↗
PubMed1997

Non-syndromic dominant sensorineural hearing loss: from a few phenotypes to many genotypes.

Sensorineural hearing loss affects approximately 1 in 2 persons at about 80 years of age and 1 in 750 in childhood. The best known forms of hearing loss with an autosomal dominant pattern of inheritance are the syndromic-mediated ones. At present, the non-syndromic autosomal dominant inherited forms can only be distinguished by the shape of the tone-audiogram. Based on gene linkage studies twelve different genotypes for autosomal dominant hereditary non-syndromic forms of sensorineural hearing loss have been recognized in a period of almost 2 years. In view of the great diversity of types that have been recognized in such a short period, it can be expected that over the next 10 years, several dozens genetically-mediated forms of autosomal dominant inherited sensorineural hearing loss will be detected. Similar developments are taking place in the non-syndromic autosomal recessive hereditary forms of sensorineural hearing loss and deafness. The above indicates clearly that before too long, new genetic investigation techniques will enable us to distinguish between forms of sensorineural hearing loss that could not be distinguished in the past.

Chromosome Aberrations↗
PubMed1997

Inherited nonsyndromic hearing loss. An audiovestibular study in a large family with autosomal dominant progressive hearing loss related to DFNA2.

OBJECTIVE: To study nonsyndromic progressive sensorineural hearing loss (SNHL) with significant linkage to the DFNA2 locus on chromosome 1p in a Dutch kindred. DESIGN: A 6-generation family with 194 family members was studied. Of the presumably affected persons, 43 were examined in detail to obtain audiograms and 37 underwent vestibulo-ocular examination. RESULTS: Regression analysis showed significant and equal linear progression in SNHL with age (by about 1 dB per year) at all frequencies. Offset values were close to zero at the low frequencies (0.25, 0.5, and 1 kHz) but increased systematically with the frequency. It is likely that they represent congenital high-frequency SNHL: about 15 dB at 2 kHz, 30 dB at 4 kHz, and 50 dB at 8 kHz. Bilateral caloric weakness was not observed. A significant finding was that 25% to 35% (depending on the exclusion criteria) of the patients showed an increased vestibulo-ocular reflex (hyperreactivity) as measured by rotatory responses. Forty-one patients showed significant linkage to the 1p locus. CONCLUSIONS: Including the present family, 4 families have been reported to show linkage to chromosome 1p. Statistical analysis of the audiological data shows a progression of 1 dB per octave per year in this type of progressive SNHL.

Adult↗
PubMed1996

Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients.

Usher syndrome type 1b (USH1B) is an autosomal recessive disorder characterized by congenital profound hearing loss, vestibular abnormalities, and retinitis pigmentosa. The disorder has recently been shown to be caused by mutations in the myosin VIIa gene (MYO7A) located on 11q14. In the current study, a panel of 189 genetically independent Usher I cases were screened for the presence of mutations in the N-terminal coding portion of the motor domain of MYO7A by heteroduplex analysis of 14 exons. Twenty-three mutations were found segregating with the disease in 20 families. Of the 23 mutations, 13 were unique, and 2 of the 13 unique mutations (Arg212His and Arg212Cys) accounted for the greatest percentage of observed mutant alleles (8/23, 31%). Six of the 13 mutations caused premature stop codons, 6 caused changes in the amino acid sequence of the myosin VIIa protein, and 1 resulted in a splicing defect. Three patients were homozygotes or compound heterozygotes for mutant alleles; these three cases were Tyr333Stop/Tyr333Stop, Arg212His-Arg302His/Arg212His-Arg302His, and IVS13nt-8c-->g/Glu450Gln. All the other USH1B mutations observed were simple heterozygotes, and it is presumed that the mutation on the other allele is present in the unscreened regions of the gene. None of the mutations reported here were observed in 96 unrelated control samples, although several polymorphisms were detected. These results add three patients to single case reported previously where mutations have been found in both alleles and raises the total number of unique mutations in MYO7A to 16.

Alleles↗
PubMed1995

Clinical findings in obligate carriers of type I Usher syndrome.

Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal pure-tone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electro-oculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities.

Adult↗
PubMed1989

Stapes surgery in osteogenesis imperfecta.

Between 1968 and 1986 stapes surgery has been performed in the Nijmegen University Department of Otorhinolaryngology in 11 patients (14 ears) with osteogenesis imperfecta. Detailed information about pre- and postoperative hearing levels, findings at surgery, and the follow-up period are presented. In most cases the stapedectomy has been successful.

Follow-Up Studies↗
PubMed1987

Autosomal recessive progressive high-frequency sensorineural deafness in childhood.

Autosomal recessive progressive high-frequency sensorineural deafness in childhood occurred in six patients from two families. This progressive sensorineural hearing loss starts mainly in the higher frequencies. There is an abrupt decline in the audiogram that slowly decreases with the increase of the hearing loss in the lower frequencies.

Adult↗
PubMed1985

Proximal symphalangia and stapes ankylosis.

A father and his two sons had an autosomal-dominant syndrome of proximal symphalangia and conductive hearing loss. Exploratory tympanotomy revealed a congenitally fixed stapes and incus in the oldest boy. Surgical intervention resulted in normal hearing. To our knowledge, this is the first such histologic report of a stapes in this syndrome.

Adolescent↗